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dc.contributor.author
Ghiglione, Barbara
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Rodríguez, María Margarita
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Herman, Raphaël
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Curto, Lucrecia María
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Dropa, Milena
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Bouillenne, Fabrice
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Kerff, Frédéric
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Galleni, Moreno
dc.contributor.author
Charlier, Paulette
dc.contributor.author
Gutkind, Gabriel Osvaldo
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Sauvage, Eric
dc.contributor.author
Power, Pablo
dc.date.available
2018-03-14T20:18:19Z
dc.date.issued
2015-07
dc.identifier.citation
Ghiglione, Barbara; Rodríguez, María Margarita; Herman, Raphaël; Curto, Lucrecia María; Dropa, Milena; et al.; Structural and Kinetic Insights into the "Ceftazidimase" Behavior of the Extended-Spectrum β-Lactamase CTX-M-96; American Chemical Society; Biochemistry; 54; 32; 7-2015; 5072-5082
dc.identifier.issn
0006-2960
dc.identifier.uri
http://hdl.handle.net/11336/38803
dc.description.abstract
Diversification of the CTX-M β-lactamases led to the emergence of variants responsible for decreased susceptibility to ceftazidime, like the Asp240Gly-harboring "ceftazidimases". We solved the crystallographic structure of the Asp240Gly variant CTX-M-96 at 1.2 Å and evaluated the role of Asp240 in the activity toward oxyimino-cephalosporins through simulated models and kinetics. There seem to be subtle changes in the conformation of the active site cavity of CTX-M-96, compared to enzyme variants harboring the Asp240, and these small rearrangements could be due to localized shifts in the environment of the β3 strand. According to the crystallographic evidence, CTX-M-96 presents a "compact" active site, which in spite of its reduced cavity seems to allow the proper interaction with oxyimino-cephalosporins, as suggested by simulated models. The term "ceftazidimases" that is currently applied for the Asp240Gly-harboring CTX-M variants should be used carefully. Structural differences between CTX-M harboring the Asp240Gly mutation (and also probably others like those at Pro167) do not seem to be conclusive to determine the "ceftazidimase" behavior observed in vivo, which is in turn partially supported by the mild improvement in the catalytic efficiency toward ceftazidime by CTX-M-96 and similar enzymes, compared to "parental" Asp240-harboring variants. In addition, it is observed that alterations in OmpF expression could act synergistically with CTX-M-96 for yielding clinical resistance toward ceftazidime. We therefore propose that the observed resistance in vivo is due to the sum of synergic mechanisms, and the term "cefotaximases associated with ceftazidime resistance" could be conveniently used to describe CTX-M harboring the Asp240Gly substitution.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
X-Ray Crystallography
dc.subject
Asp240gly
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Oxyimino-Cephalosporins
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Class a Β- Lactamase
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Enterobacteriaceae
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Antimicrobial Resistance
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Ompf
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Structural and Kinetic Insights into the "Ceftazidimase" Behavior of the Extended-Spectrum β-Lactamase CTX-M-96
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-13T13:58:06Z
dc.journal.volume
54
dc.journal.number
32
dc.journal.pagination
5072-5082
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Rodríguez, María Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Herman, Raphaël. Université de Liège; Bélgica
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Fil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
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Fil: Dropa, Milena. Universidade de Sao Paulo; Brasil
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Fil: Bouillenne, Fabrice. Université de Liège; Bélgica
dc.description.fil
Fil: Kerff, Frédéric. Université de Liège; Bélgica
dc.description.fil
Fil: Galleni, Moreno. Université de Liège; Bélgica
dc.description.fil
Fil: Charlier, Paulette. Université de Liège; Bélgica
dc.description.fil
Fil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
dc.description.fil
Fil: Sauvage, Eric. Université de Liège; Bélgica
dc.description.fil
Fil: Power, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
dc.journal.title
Biochemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acs.biochem.5b00313
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/acs.biochem.5b00313
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